title: The effect of oxysterols on the interaction of Alzheimer's amyloid beta with model membranes.
abstract: The interaction of amyloid beta (Aβ) peptide with cell membranes has been shown to be influenced by Aβ conformation, membrane physicochemical properties and lipid composition. However, the effect of cholesterol and its oxidized derivatives, oxysterols, on Aβ-induced neurotoxicity to membranes is not fully understood. We employed here model membranes to investigate the localization of Aβ in membranes and the peptide-induced membrane dynamics in the presence of cholesterol and 7-ketocholesterol (7keto) or 25-hydroxycholesterol (25OH). Our results have indicated that oxysterols rendered membranes more sensitive to Aβ, in contrast to role of cholesterol in inhibiting Aβ/membrane interaction. We have demonstrated that two oxysterols had different impacts owing to distinct positions of the additional oxygen group in their structures. 7keto-containing cell-sized liposomes exhibited a high propensity toward association with Aβ, while 25OH systems were more capable of morphological changes in response to the peptide. Furthermore, we have shown that 42-amino acid Aβ (Aβ-42) pre-fibril species had higher association with membranes, and caused membrane fluctuation faster than 40-residue isoform (Aβ-40). These findings suggest the enhancing effect of oxysterols on interaction of Aβ with membranes and contribute to clarify the harmful impact of cholesterol on Aβ-induced neurotoxicity by means of its oxidation.
authors.affiliation: School of Materials Science, Japan Advanced Institute of Science and Technology (JAIST), 1-1 Asahidai, Nomi, Ishikawa 923-1292, Japan.
authors.forename: Huong T T
authors.initials: HT
authors.lastname: Phan
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hata
authors.forename: Masamune
authors.initials: M
authors.lastname: Morita
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yoda
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hamada
authors.forename: Mun'delanji C
authors.initials: MC
authors.lastname: Vestergaard
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takagi
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D002784:Cholesterol / Q000031:analogs & derivatives / Q000737:chemistry*; D008081:Liposomes; D008567:Membranes, Artificial
chemical_list: D016229:Amyloid beta-Peptides; D008081:Liposomes; D008567:Membranes, Artificial; D002784:Cholesterol
keywords: Amyloid beta; Aβ localization; Membrane dynamics; Model membranes; Oxysterols